Interactions between NSAIDs, opioids and the gut microbiota- Future perspectives in the management of inflammation and pain

The composition of intestinal microbiota is influenced by a number of factors, including medications, which may have a substantial impact on host physiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid anal-gesics are among those widely used medications that have been shown to alter microbiota composition in both animals and humans. Although much effort has been devoted to identify microbiota signatures associated with these medications, much less is known about the underlying mechanisms. Mucosal inflammation, changes in intestinal motility, luminal pH and bile acid metabolism, or direct drug-induced inhibitory effect on bacterial growth are all potential contributors to NSAID-and opioid-induced dysbiosis, however, only a few studies have addressed directly these issues. In addition, there is a notable overlap between the microbiota signatures of these drugs and certain diseases in which they are used, such as spondyloarthritis (SpA), rheumatoid arthritis (RA) and neuropathic pain associated with type 2 diabetes (T2D). The aims of the present review are threefold. First, we aim to provide a comprehensive up-to-date summary on the bacterial alterations caused by NSAIDs and opioids. Second, we critically review the available data on the possible underlying mechanisms of dysbiosis. Third, we review the current knowledge on gut dysbiosis associated with SpA, RA and neuropathic pain in T2D, and highlight the similarities between them and those caused by NSAIDs and opioids. We posit that drug -induced dysbiosis may contribute to the persistence of these diseases, and may potentially limit the therapeutic effect of these medications by long-term use. In this context, we will review the available literature data on the effect of probiotic supplementation and fecal microbiota transplantation on the therapeutic efficacy of NSAIDs and opioids in these diseases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Automated summary

The composition of intestinal microbiota can be affected by medications such as NSAIDs and opioids, leading to dysbiosis. The underlying mechanisms of dysbiosis caused by these drugs are not well understood, but mucosal inflammation, changes in motility and pH, and direct drug effect on bacterial growth are possible contributors. The microbiota signatures of NSAIDs and opioids overlap with certain diseases like SpA, RA, and neuropathic pain in T2D. Drug-induced dysbiosis may contribute to the persistence of these diseases and limit the therapeutic effect of these medications. Probiotic supplementation and fecal microbiota transplantation may have an impact on the therapeutic efficacy of NSAIDs and opioids in these diseases.